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Fulltext Molecular Classification, Treatment, and Genetic Biomarkers in Triple-Negative Breast Cancer: A Review

Lu B, Natarajan E, Balaji Raghavendran HR, Markandan UD

Technol Cancer Res Treat, 2023;22:15330338221145246.
PMID: 36601658 DOI: 10.1177/15330338221145246

Breast cancer is the most common malignancy and the second most common cause of cancer-related mortality in women. Triple-negative breast cancers do not express estrogen receptors, progesterone receptors, or human epidermal growth factor receptor 2 and have a higher recurrence rate, greater metastatic potential, and lower overall survival rate than those of other breast cancers. Treatment of triple-negative breast cancer is challenging; molecular-targeted therapies are largely ineffective and there is no standard treatment. In this review, we evaluate current attempts to classify triple-negative breast cancers based on their molecular features. We also describe promising treatment methods with different advantages and discuss genetic biomarkers and other prediction tools. Accurate molecular classification of triple-negative breast cancers is critical for patient risk categorization, treatment decisions, and surveillance. This review offers new ideas for more effective treatment of triple-negative breast cancer and identifies novel targets for drug development.
Genetic and structural characterization of 20 autosomal short tandem repeats in the Chinese Qinghai Han population and its genetic relationships and interpopulation differentiations with other reference populations

Wang Z, Lu B, Jin X, Yan J, Meng H, Zhu B

Forensic Sci Res, 2018;3(2):145-152.
PMID: 30483663 DOI: 10.1080/20961790.2018.1485199

China is a multinational country composed of 56 ethnic groups of which the Han Chinese accounts for 91.60%. Qinghai Province is located in the northeastern part of the Qinghai-Tibet Plateau, has an area of 72.12 km2, and is the fourth largest province in China. In the present study, we investigated the genetic polymorphisms of 20 short tandem repeat (STR) loci in a Qinghai Han population, as well as its genetic relationships with other populations. A total of 273 alleles were identified in 2 000 individuals at 20 loci, and the allelic frequency ranged from 0.000 2 to 0.532 7. The 20 STR loci showed a relatively high polymorphic rate in the studied group. Observed and expected heterozygosities ranged 0.613 0-0.907 5 and 0.614 8-0.920 0, respectively. The combined power of discrimination, and the probability of exclusion in duo and trio cases were 0.999 999 999 999 999 999 999 999 34, 0.999 996 0 and 0.999 999 996 5, respectively. Analyses of interpopulation differentiation revealed that the most significant differences were found between the Qinghai Han and Malaysian, while no significant differences were found between the Qinghai Han and Han people from Shaanxi and Jiangsu. The results of principal component analysis, multidimensional scaling analysis and phylogenetic reconstructions also suggested the close relationships between the Qinghai Han and other two Han populations. The present results, therefore, indicated that these 20 STR loci could be used for paternity testing and individual identification in forensic applications, and may also provide information for the studies of genetic relationships between Qinghai Han and other groups.
Detection of microRNA-335-5p on an Interdigitated Electrode Surface for Determination of the Severity of Abdominal Aortic Aneurysms

Lu B, Liu L, Wang J, Chen Y, Li Z, Gopinath SCB, et al.

Nanoscale Res Lett, 2020 May 11;15(1):105.
PMID: 32394009 DOI: 10.1186/s11671-020-03331-y

Abdominal aortic aneurysm (AAA) refers to the enlargement of the lower artery of the abdominal aorta, and identification of an early detection tool is urgently needed for diagnosis. In the current study, an interdigitated electrode (IDE) sensing surface was used to identify miRNA-335-5p, which reflects the formation of AAAs. The uniformity of the silica material was observed by 3D profilometry, and the chemically modified highly conductive surface improved the detection via the I-V mode. The targeted miRNA-335-5p was detected in a dose-dependent manner and based on linear regression and 3σ analyses, the sensitivity was determined to be 1 fM with a biotinylated probe. The high specificity was shown by discriminating the target sequence from noncomplementary and single- and triple-mismatched sequences. These outputs demonstrated the high-performance detection of miRNA-335-5p with good reproducibility for determination of the severity of AAA.
Clone, expression and plasminogen binding property of three fructose-1,6-bisphosphate aldolases from Clonorchis sinensis

Li S, Lu BP, Feng J, Zhou JJ, Xie ZZ, Liang C, et al.

Trop Biomed, 2020 Dec 01;37(4):852-863.
PMID: 33612738 DOI: 10.47665/tb.37.4.852

Fructose-1,6-bisphosphate aldolase (FbA), a well characterized glycometabolism enzyme, has been found to participate in other important processes besides the classic catalysis. To understand the important functions of three fructose-1,6-bisphosphate aldolases from Clonorchis sinensis (CsFbAs, CsFbA-1/2/3) in host-parasite interplay, the open reading frames of CsFbAs were cloned into pET30a (+) vector and the resulting recombinant plasmids were transformed into Escherichia coli BL21 (DE3) for expression of the proteins. Purified recombinant CsFbAs proteins (rCsFbAs) were approximately 45.0 kDa on 12% SDS-PAGE and could be probed with each rat anti-rCsFbAs sera by western blotting analysis. ELISA and ligand blot overlay indicated that rCsFbAs of 45.0 kDa as well as native CsFbAs of 39.5 kDa from total worm extracts and excretory-secretory products of Clonorchis sinensis (CsESPs) could bind to human plasminogen, and the binding could be efficiently inhibited by lysine analog ε-aminocaproic acid. Our results suggested that as both the components of CsESPs and the plasminogen binding proteins, three CsFbAs might be involved in preventing the formation of the blood clot so that Clonorchis sinensis could acquire enough nutrients from host tissue for their successful survival and colonization in the host. Our work will provide us with new information about the biological function of three CsFbAs and their roles in hostparasite interplay.
Fulltext Synthesis of Low-Cost and High-Performance Dual-Atom Doped Carbon-Based Materials with a Simple Green Route as Anodes for Sodium-Ion Batteries

Lu B, Zhang C, Deng DR, Weng JC, Song JX, Fan XH, et al.

Molecules, 2023 Oct 28;28(21).
PMID: 37959733 DOI: 10.3390/molecules28217314

Sodium-ion batteries (SIBs) are promising alternatives to replace lithium-ion batteries as future energy storage batteries because of their abundant sodium resources, low cost, and high charging efficiency. In order to match the high energy capacity and density, designing an atomically doped carbonous material as the anode is presently one of the important strategies to commercialize SIBs. In this work, we report the preparation of high-performance dual-atom-doped carbon (C) materials using low-cost corn starch and thiourea (CH4N2S) as the precursors. The electronegativity and radii of the doped atoms and C are different, which can vary the embedding properties of sodium ions (Na+) into/on C. As sulfur (S) can effectively expand the layer spacing, it provides more channels for embedding and de-embedding Na+. The synergistic effect of N and S co-doping can remarkably boost the performance of SIBs. The capacity is preserved at 400 mAh g -1 after 200 cycles at 500 mA g-1; more notably, the initial Coulombic efficiency is 81%. Even at a high rate of high current of 10 A g-1, the cell capacity can still reach 170 mAh g-1. More importantly, after 3000 cycles at 1 A g-1, the capacity decay is less than 0.003% per cycle, which demonstrates its excellent electrochemical performance. These results indicate that high-performance carbon materials can be prepared using low-cost corn starch and thiourea.
Fulltext Hard-Carbon Negative Electrodes from Biomasses for Sodium-Ion Batteries

Lu B, Lin C, Xiong H, Zhang C, Fang L, Sun J, et al.

Molecules, 2023 May 11;28(10).
PMID: 37241775 DOI: 10.3390/molecules28104027

With the development of high-performance electrode materials, sodium-ion batteries have been extensively studied and could potentially be applied in various fields to replace the lithium-ion cells, owing to the low cost and natural abundance. As the key anode materials of sodium-ion batteries, hard carbons still face problems, such as poor cycling performance and low initial Coulombic efficiency. Owning to the low synthesis cost and the natural presence of heteroatoms of biomasses, biomasses have positive implications for synthesizing the hard carbons for sodium-ion batteries. This minireview mainly explains the research progress of biomasses used as the precursors to prepare the hard-carbon materials. The storage mechanism of hard carbons, comparisons of the structural properties of hard carbons prepared from different biomasses, and the influence of the preparation conditions on the electrochemical properties of hard carbons are introduced. In addition, the effect of doping atoms is also summarized to provide an in-depth understanding and guidance for the design of high-performance hard carbons for sodium-ion batteries.
Fulltext 2017 Multimodality Appropriate Use Criteria for Noninvasive Cardiac Imaging: Expert Consensus of the Asian Society of Cardiovascular Imaging

ASCI Practice Guideline Working Group, Beck KS, Kim JA, Choe YH, Sim KH, Hoe J, et al.

Korean J Radiol, 2017 Nov-Dec;18(6):871-880.
PMID: 29089819 DOI: 10.3348/kjr.2017.18.6.871

In 2010, the Asian Society of Cardiovascular Imaging (ASCI) provided recommendations for cardiac CT and MRI, and this document reflects an update of the 2010 ASCI appropriate use criteria (AUC). In 2016, the ASCI formed a new working group for revision of AUC for noninvasive cardiac imaging. A major change that we made in this document is the rating of various noninvasive tests (exercise electrocardiogram, echocardiography, positron emission tomography, single-photon emission computed tomography, radionuclide imaging, cardiac magnetic resonance, and cardiac computed tomography/angiography), compared side by side for their applications in various clinical scenarios. Ninety-five clinical scenarios were developed from eight selected pre-existing guidelines and classified into four sections as follows: 1) detection of coronary artery disease, symptomatic or asymptomatic; 2) cardiac evaluation in various clinical scenarios; 3) use of imaging modality according to prior testing; and 4) evaluation of cardiac structure and function. The clinical scenarios were scored by a separate rating committee on a scale of 1-9 to designate appropriate use, uncertain use, or inappropriate use according to a modified Delphi method. Overall, the AUC ratings for CT were higher than those of previous guidelines. These new AUC provide guidance for clinicians choosing among available testing modalities for various cardiac diseases and are also unique, given that most previous AUC for noninvasive imaging include only one imaging technique. As cardiac imaging is multimodal in nature, we believe that these AUC will be more useful for clinical decision making.
Fulltext Toward Sustainable Environmental Quality: Priority Research Questions for Asia

Leung KMY, Yeung KWY, You J, Choi K, Zhang X, Smith R, et al.

Environ Toxicol Chem, 2020 Aug;39(8):1485-1505.
PMID: 32474951 DOI: 10.1002/etc.4788

Environmental and human health challenges are pronounced in Asia, an exceptionally diverse and complex region where influences of global megatrends are extensive and numerous stresses to environmental quality exist. Identifying priorities necessary to engage grand challenges can be facilitated through horizon scanning exercises, and to this end we identified and examined 23 priority research questions needed to advance toward more sustainable environmental quality in Asia, as part of the Global Horizon Scanning Project. Advances in environmental toxicology, environmental chemistry, biological monitoring, and risk-assessment methodologies are necessary to address the adverse impacts of environmental stressors on ecosystem services and biodiversity, with Asia being home to numerous biodiversity hotspots. Intersections of the food-energy-water nexus are profound in Asia; innovative and aggressive technologies are necessary to provide clean water, ensure food safety, and stimulate energy efficiency, while improving ecological integrity and addressing legacy and emerging threats to public health and the environment, particularly with increased aquaculture production. Asia is the largest chemical-producing continent globally. Accordingly, sustainable and green chemistry and engineering present decided opportunities to stimulate innovation and realize a number of the United Nations Sustainable Development Goals. Engaging the priority research questions identified herein will require transdisciplinary coordination through existing and nontraditional partnerships within and among countries and sectors. Answering these questions will not be easy but is necessary to achieve more sustainable environmental quality in Asia. Environ Toxicol Chem 2020;39:1485-1505. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Fulltext A multimodal atlas of hepatocellular carcinoma reveals convergent evolutionary paths and 'bad apple' effect on clinical trajectory

Chen J, Kaya NA, Zhang Y, Kendarsari RI, Sekar K, Lee Chong S, et al.

J Hepatol, 2024 May 21.
PMID: 38782118 DOI: 10.1016/j.jhep.2024.05.017

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a highly fatal cancer characterized by high intra-tumor heterogeneity (ITH). A panoramic understanding of its tumor evolution, in relation to its clinical trajectory, may provide novel prognostic and treatment strategies.
METHODS: Through the Asia-Pacific Hepatocellular Carcinoma trials group (NCT03267641), we recruited one of the largest prospective cohorts of patients with HCC, with over 600 whole genome and transcriptome samples from 123 treatment-naïve patients.
RESULTS: Using a multi-region sampling approach, we revealed seven convergent genetic evolutionary paths governed by the early driver mutations, late copy number variations and viral integrations, which stratify patient clinical trajectories after surgical resection. Furthermore, such evolutionary paths shaped the molecular profiles, leading to distinct transcriptomic subtypes. Most significantly, although we found the coexistence of multiple transcriptomic subtypes within certain tumors, patient prognosis was best predicted by the most aggressive cell fraction of the tumor, rather than by overall degree of transcriptomic ITH level - a phenomenon we termed the 'bad apple' effect. Finally, we found that characteristics throughout early and late tumor evolution provide significant and complementary prognostic power in predicting patient survival.
CONCLUSIONS: Taken together, our study generated a comprehensive landscape of evolutionary history for HCC and provides a rich multi-omics resource for understanding tumor heterogeneity and clinical trajectories.
IMPACT AND IMPLICATIONS: This prospective study, utilizing comprehensive multi-sector, multi-omics sequencing and clinical data from surgically resected hepatocellular carcinoma (HCC), reveals critical insights into the role of tumor evolution and intra-tumor heterogeneity (ITH) in determining the prognosis of HCC. These findings are invaluable for oncology researchers and clinicians, as they underscore the influence of distinct evolutionary paths and the 'bad apple' effect, where the most aggressive tumor fraction dictates disease progression. These insights not only enhance prognostic accuracy post-surgical resection but also pave the way for personalized treatment strategies tailored to specific tumor evolutionary and transcriptomic profiles. The coexistence of multiple subtypes within the same tumor prompts a re-appraisal of the utilities of depending on single samples to represent the entire tumor and suggests the need for clinical molecular imaging. This research thus marks a significant step forward in the clinical understanding and management of HCC, underscoring the importance of integrating tumor evolutionary dynamics and multi-omics biomarkers into therapeutic decision-making.
CLINICAL TRIAL NUMBER: NCT03267641 (Observational cohort).
Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.

Autophagy, 2016;12(1):1-222.
PMID: 26799652 DOI: 10.1080/15548627.2015.1100356